There are many memory-related conditions for which therapeutic treatments are under investigation, such as methods to enhance memory or to treat memory dysfunction. Memory dysfunction is believed to be linked to the aging process, as well as to neurodegenerative diseases such as Alzheimer's disease. Also, memory impairment can follow head trauma or multi-infarct dementia. Many compounds and treatments have been investigated which can enhance cognitive processes, that is, which can improve memory and retention.
The compound piracetam has been prescribed for treatment to enhance memory [Giurgea et al, Arch. Int. Pharmacodyn. Ther., 166, 238 (1967)]. U.S. Pat. No. 4,639,468 to Roncucci et al describes the compound milacemide which is mentioned as useful for treatment of memory troubles. Further investigations of milacemide have documented the memory-enhancing capabilities of milacemide in human subjects [B. Saletu et al, Arch. Gerontol, Geriatr., 5, 165-181 (1986 )].
The effects of milacemide on memory have been correlated with the increase in brain glycine content which follows milacemide administration. This specific glycine effect is suspected to be mediated through the recently discovered strychnine-insensitive glycine receptor (also known as the "Glycine B" receptor site) [J. B. Monahan et al., J. Neurochemistry, 53, 370-375 (1989)]. So far the structure-activity relationships developed around this receptor have shown that the highest affinities are obtained with small, hydrophilic amino acids of the D-isomer configuration such as D-serine and D-alanine [L. D. Snell et al., Eur. J. Pharmacol., 156, 105-110 (1988)] and aminocyclopropyl carboxylic acid ["ACC"; V. Nadler et al., Eur. J. Pharmacol., 157, 115-116 (1988)].
Certain vinyl glycine derivatives have been reported as antibiotics and enzyme inhibitors. For example, the inhibition of bacterial methionine-.gamma.-lyase by L-2-amino-3-trans-pentenoate has been reported [M. Johnson et al., Biochemistry, 20, 4325-4333 (1981)]. Also, the compound L-2-amino-4-methoxy-trans-3-butenoic acid, isolated from Pseudomonas aeruginosa, has been shown to be an irreversible inhibitor of the L-aspartate aminotransferase enzyme [R. R. Rando, Nature, 250, 587-588 (1974)].